Lymphosarcoma is a group of malignant cancers of the lymphoid tissue. Mouse lymphosarcoma cell lines, RAW117 and PU15, closely parallel highly malignant human lymphosarcoma (malignant lymphocytoma) in cell type, disease course, tumor distribution and organ involvement. We will develop metastatic variant cell lines of RAW117 and PU15 by sequential in vivo, as well as in vitro, selection methods to obtain stable tumor cell variant lines of differing malignant potentials and organ preferences. We have successfully selected in vivo for liver-preferring RAW117 variants of high metastatic potential, and we have used nonadherence to immobolized-lectins to select lectin attachment variants with differing cell surface properties and metastatic potentials. The cell surface of these variant cell lines will be examined and compared to parental cell lines for biochemical, immunological, morphological and enzymatic changes to determine which cell surface characteristics are important in lymphosarcoma malignancy and its metastatic distribution in vivo. Attempts will be made to use this information to block or modify the extent, location and course of highly malignant lymphosarcoma in syngeneic hosts. In addition, a common problem in lymphosarcoma treatment is acquired resistance to chemotherapy. The sensitivities of these different malignant variant lines to chemotherapeutic drug, such as alkylating agents, hormones and antimetabolites, will be determined, and drug resistant variants will be selected in vitro and analyzed. The cell surfaces of the drug-resistant lines will be compared with drug-sensitive lines to see if cell surface characteristics are modified when the cells acquire resistance and determine the possible differences between resistant and sensitive cell lines of differing in vivo metastatic potentials.